Éditeur(s) : HAL CCSD
Résumé : International audience
OBJECTIVES: Semen composition is influenced by HIV-1 infection, yet the impact of semen components on HIV infection of primary target cells has only been studied in samples from HIV-uninfected donors. DESIGN: We compared the effect of seminal plasma from chronically HIV-infected (SP+) versus uninfected donors (SP-) on HIV-1 infection of PBMCs and CD4+T cells. METHODS: Primary cells were infected with HIV-1 in the presence of SP+ or SP- and analyzed for infection level, metabolic activity, HIV receptor expression, proliferation and activation. SP+ and SP- were compared for infection-enhancing peptides, cytokines and prostaglandin E2 levels. RESULTS: SP- efficiently enhanced HIV-1 R5 infection of CD4+ T cells, whereas SP+ enhancing activity was significantly reduced. RANTES concentrations were elevated in SP+ relative to SP-, while the concentrations of infectivity-enhancing peptides (SEVI, SEM1, SEM2) were similar. CCR5 membrane expression levels were reduced on CD4+T cells shortly post-exposure to SP+ compared with SP- and correlated to R5-tropic HIV-1 infection levels, and CCR5 ligands' concentrations in semen. SP+ and SP- displayed similar enhancing activity on PBMC infection by X4-tropic HIV-1. Addition/depletion of RANTES from seminal plasmas modulated their effect on PBMC infection by R5-tropic HIV-1. CONCLUSIONS: Semen from HIV-infected donors exhibit a significantly reduced enhancing potential on CD4+ T cell infection by R5-tropic HIV-1 when compared with semen from uninfected donors. Our data indicate that elevated seminal concentrations of RANTES in HIV+ men can influence the ability of semen to enhance infection.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives 4.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0
AIDS

hal-01274885
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01274885
DOI : 10.1097/QAD.0000000000001048
PUBMED : 26854806

Éditeur(s) : HAL CCSD WB Saunders
Résumé : International audience
OBJECTIVE: We hypothesized that, in Human Immunodeficiency Virus and Hepatitis C Virus (HIV/HCV) co-infected patients who did not respond to peg-interferon and ribavirin, a maintenance therapy with peg-interferon could induce fibrosis regression. METHODS: This was a randomized study with two parallel groups. HIV/HCV co-infected patients received peg-interferon α-2a at 180 μg/week or remained on observation for 96 weeks. The primary endpoint was the percentage of patients who experienced a decrease of at least one point in their Metavir fibrosis score between initial and final liver biopsies. Secondary endpoints included plasma fibrosis markers at week 96, occurrence of HCV-related complications, and survival. RESULTS: A total of 52 patients were randomized (peg-interferon: 25; control: 27) including 18 with cirrhosis. The median (interquartile range) age was 44 (40-46) years, and 69% were male. A total of 64% had ALT levels >1.5 normal values, and the CD4 cell count was 391 (296-537) cells/mm(3); 67% of patients had HIV RNA <200 copies/mL at entry. The main endpoint was assessed in 41 patients. Response rates were 3/20 (15%) and 4/21 (19%) in the peg-interferon and control groups, respectively (p = 0.99). There was no significant difference between peg-interferon and control groups on plasma fibrosis markers at the final visit. Severe liver-related complications were observed in 2 and 5 patients in peg-interferon and control groups, respectively. Three deaths were observed, all in the control group. CONCLUSIONS: A maintenance therapy with peg-interferon α-2a over 96 weeks in HIV/HCV co-infected patients, who were non-responders to HCV treatment, did not change liver fibrosis. ClinicalTrials.gov Identifier: NCT00122616.
ISSN: 0163-4453

hal-00875067
https://hal.archives-ouvertes.fr/hal-00875067
DOI : 10.1016/j.jinf.2013.05.007
PUBMED : 23800784

Éditeur(s) : HAL CCSD American Society of Tropical Medicine and Hygiene
Résumé : International audience
Histoplasmosis is the first cause of acquired immunodeficiency syndrome (AIDS) and AIDS-related deaths in French Guiana. Cohort data were used to determine whether primary prophylaxis with 100 mg itraconazole for patients with CD4 counts < 150/mm(3) was cost-effective with different scenarios. For a scenario where 12% of patients died, 60% were aware of their human immunodeficiency virus (HIV) infection and adherence was only 50%, primary prophylaxis would prevent 1 death and 9 cases of histoplasmosis for a cost of 36,792 Euros per averted death, 1,533 per life-year saved, 4,415 Euros per averted case, when only counting the costs of itraconazole prophylaxis. Taking into account the total costs of hospitalization showed that primary prophylaxis would allow a savings of 185,178 Euros per year. Even in a scenario of low adherence, primary prophylaxis would be cost-effective in French Guiana, and presumably in the rest of the Guianas and the Amazon.
ISSN: 0002-9637

inserm-00913886
http://www.hal.inserm.fr/inserm-00913886
http://www.hal.inserm.fr/inserm-00913886/document
http://www.hal.inserm.fr/inserm-00913886/file/2013_Nacher_-_Primary_prophylaxissur disseminated_histoplasmosis_in_HIV_patients_in_French_Guiana_a_cost_effectiveness_study.pdf
DOI : 10.4269/ajtmh.13-0082

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathways
ISSN: 1553-7366

Droits : http://creativecommons.org/licenses/by/
hal-01207287
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207287
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207287/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207287/file/journal.ppat.1005153.pdf
DOI : 10.1371/journal.ppat.1005153

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4(+) T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4(+) T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure.
ISSN: 1553-7366

hal-00955292
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00955292
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00955292/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00955292/file/Semen_CD4_T-accepted.pdf
PUBMED : 24348253

Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
BACKGROUND: Chronic HCV infection is associated with the development of hepatic fibrosis. The direct role of HCV in the fibrogenic process is unknown. Specifically, whether HCV is able to infect hepatic stellate cells (HSCs) is debated. OBJECTIVE: To assess whether human HSCs are susceptible to HCV infection. DESIGN: We combined a set of original HCV models, including the infectious genotype 2a JFH1 model (HCVcc), retroviral pseudoparticles expressing the folded HCV genotype 1b envelope glycoproteins (HCVpp) and a subgenomic genotype 1b HCV replicon, and two relevant cellular models, primary human HSCs from different patients and the LX-2 cell line, to assess whether HCV can infect/replicate in HSCs. RESULTS: In contrast with the hepatocyte cell line Huh-7, neither infectious HCVcc nor HCVpp infected primary human HSCs or LX-2 cells. The cellular expression of host cellular factors required for HCV entry was high in Huh-7 cells but low in HSCs and LX-2 cells, with the exception of CD81. Finally, replication of a genotype 2a full-length RNA genome and a genotype 1b subgenomic replicon was impaired in primary human HSCs and LX-2 cells, which expressed low levels of cellular factors known to play a key role in the HCV life-cycle, suggesting that human HSCs are not permissive for HCV replication. CONCLUSIONS: Human HSCs are refractory to HCV infection. Both HCV entry and replication are deficient in these cells, regardless of the HCV genotype and origin of the cells. Thus, HCV infection of HSCs does not play a role in liver fibrosis. These results do not rule out a direct role of HCV infection of hepatocytes in the fibrogenic process.
ISSN: 0017-5749

hal-01063909
https://hal.archives-ouvertes.fr/hal-01063909
DOI : 10.1136/gutjnl-2013-305634
PUBMED : 25063678

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Malaria is a major public health problem in French Guiana, where Plasmodium vivax has become the dominant malaria species since 2000. As in others endemic areas, it is important to specify the pattern of vivax malaria relapses and to try to discriminate efficiently re-infections from relapses. METHODS: This study was conducted in children born between January 1, 2001 and December 31, 2008 in Camopi, an Amerindian village located in the Amazon forest (n = 325), using an open cohort design. Primary and secondary attack rates of P. vivax were calculated using survival analysis. With the difference between the primary and secondary rates, this study aimed to estimate indirectly P. vivax relapse rate and evaluate its time evolution. RESULTS: Of the 1042 malaria attacks recorded, 689 (66%) were due to P. vivax (without mixed infection). One hundred and fifty one children had their primary attack with P. vivax and 106 had their two first attacks with P. vivax. In the absence of primaquine treatment, it was shown that P. vivax relapses mainly occurred during the first three months after the first attack. Thirty percent of children never had a relapse, 42% had a relapse before the first month after primary attack, 59% before the second month and 63% before the third month. CONCLUSION: This study confirmed that the relapse pattern in Camopi was compatible with the pattern described for the P. vivax Chesson (tropical) strain. In addition, due to the relapse rate time evolution, a simple arbitrary classification rule could be constructed: before 90 days after the primary attack, the secondary attack is a relapse; after 90 days, it is a re-infection. Adapted management of malaria cases based on these results could be devised.
ISSN: 1475-2875

inserm-00663913
http://www.hal.inserm.fr/inserm-00663913
http://www.hal.inserm.fr/inserm-00663913/document
http://www.hal.inserm.fr/inserm-00663913/file/1475-2875-8-278.pdf
DOI : 10.1186/1475-2875-8-278

Résumé : En Guyane comme dans l'ensemble de la région amazonienne, le risque de maladie de Chagas pour l'homme a longtemps été sous estimé du fait de l'absence de vecteur domestique et de l'existence d'un réservoir animal exclusivement sauvage. Le travail présenté répond aux besoins de compléter et d'actualiser les connaissances épidémiologiques disponibles sur la maladie de Chagas dans ce département , en précisant les modalités de circulation de Trypanosoma cruzi et les facteurs impliqués dans le cycle à l'origine des cas humains. Les données cumilées entre 2001 et 2023 représentent 971 spécimens de triatomes. Nous avons choisi de différencier les triatomes provenant des zones non habitées (forêts primaire ou secondaire) de ceux provenant de zones habitées, collectées dans les maisons à la faveur d'intrusion. Une espère, Panstrongylus geniculatus, s'est distinguée par son abondance (61,1%) et son omniprésence dans les différents types de milieux explorés. Au total, neuf espèces ont été retrouvées. En zone non habitée, avec une prédominance de P. geniculatus, P. lignarius, Rhodnius pictipes et R. robustus. L'infection des triatomes par T. cruzi a été étudiée, avec une mise en évidence d'un taux d'infection plus élevé chez les triatomes collectés à l'intérieur des habitations (53.9%) que chez ceux provenant des zones non habitées (46%). L'étude sur les mammifères sauvages a montré des taux d'infection élevés pour T. cruzi chez deux espèces : didelphis marsupialis (62.5%) et Philander opossum (35%). Cette étude a été complétée par l'analyse de la variabilité génétique de T. cruzi identifié par des techniques de génotypage réalisées sur du matériel obtenu à partir de triatomes, de mammifères sauvages et domestiques et des hommes. En zone non habitée trois groupes, TcI, TcII-TcV-TcVI et TcIII-TcIV, ont été caractérisés, avec une prédominance de TcI. Parmi les acteurs du cycle parasite, les chiens et P. geniculatus hébergent le groupe TcIII-TcIV à la différence du genre Rhodnius et des marsupiaux qui hébergent le groupe TcI. Nos résultats ont permis d'émettre un certain nombre d'hypothèses sur la circulation des génotypes de T. cruzi en Guyane
In French Guiana, as in the whole of Amazon region, the risk of Chagas disease to humans has long been underestimated due to the presence of non-domiciled triatomines and wild animal reservoir. Overall, this thesis aims at reactualizing and improving epidemiological knowledge about Chagas disease in French Guiana, by specific modalities of circulation of Trypanosoma cruzi and the factorsinvolved in the transmission cycle of the origin of human cases. Accumulated data, between 2001 and 2013, represent 971 triatomine specimens collected. We chose to differentiate triatomine collected in uninhabited areas (primary or secondary forests) and those frominhabited areas, collected in homes by intrusion. One species, Panstrongylus geniculatus, was distinguished by its abundance (61.1%) and its presence in different types of habitats investigated. A total of nine species were found in uninhabited area, with the predominance of four species: P. geniculatus, P. lignarius, Rhodnius pictipes and Eratyrus mucronatus. In inhabited area, five species of triatomine were collected, with the predominance of P. geniculatus, R. pictipes and R. robustus. The triatomine infection rate with T. cruzi has been studied, with a highlighting of higher rate of infection in triatomine collected inside houses (53.9%) than those from uninhabited area (46%). The study on wild mammals showed high T. cruzi infection rates for two species: Didelphis marsupialis (62.5%) and Philander opossum (35%).This study was completed by the analysis of the genetic variability of T. cruzi identified by genotyping techniques performed on material obtained from triatomine, wild and domestic mammals and humans. In uninhabited area, three groups$ TcI, TcII-TcV-TcVI and TcIII-TcIV have been characterized, with a predominance of TcIII-TcIV group. In inhabited area, only two groups were characterized (TcI andTcIII-TcIV), with a predominance of TcI. Among the actor’s transmission cycle of parasite, dogs and P. geniculatus were characterized by TcIII-TcIV group. Contrary to Rhodnius genus and marsupials were characterized by the TcI group. Our results have allowed issuing a number of assumptions about the circulation of T. cruzi genotypes in French Guiana

http://www.theses.fr/2013AGUY0734/document

Éditeur(s) : HAL CCSD
Résumé : International audience
Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (ATL). Such complications are seen frequently in L.guyanensis infections where patients respond variously to first-line anti-leishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently ,: we reported that a dsRNA virus (LRV1) nested within L.guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyper-inflammatory response. This report investigates the prevalence of LRV1 in human L.guyanensis infection and its effect on treatment efficacy as well as its correlation to symptomatic relapses after the first-line treatment. In our cohort of 75 patients diagnosed with primary-localised ATL, the prevalence of LRV1+ infection was elevated to 58%. All patients infected with LRV1-negative L.guyanensis were cured after one (22/31 i.e.71%) or two (31/31 i.e.100%) doses of pentamidine. Oppositely, 12 out of the 44 LRV1-positive patients presented with persistent infection and symptomatic relapse required extended therapy and the use of second-line drugs. Finally, LRV1 presence was associated with a significant increase in intra-lesional inflammatory markers. In conclusion, LRV1 status in L.guyanensis infection is significantly predictive (p=0.0009) of first-line treatment failure and symptomatic relapse, and could stand to guide therapeutic choices in ATL
Journal of Infectious Diseases

hal-01175528
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01175528
DOI : 10.1093/infdis/jiv355
PUBMED : 26123564

Éditeur(s) : HAL CCSD Cambridge University Press (CUP)
Résumé : International audience
Leishmania parasites can escape the immune response by invading cell types lacking leishmanicidal mechanisms. Silent persistence of Leishmania parasites in the host organism is responsible for asymptomatic carriage and relapses after cured leishmaniasis. Here, we studied the interaction between Hepatic Stellate Cells (HSC) and Leishmania. An original model of human HSC in primary culture infected with L. donovani was developed. The presence of intracellular parasites was studied and quantified using optical and confocal microscopy. HSC characteristics were studied using microscopy, methylene blue assay, long-term cultures and qPCR. We showed for the first time that human HSC are permissive to L. donovani infection, with no modification of HSC survival, growth rate and proinflammatory and fibrogenic characteristics. Intracellular parasites did not replicate but HSC had no effect on their survival. Indeed, after a 40-day culture, infected HSC cultures transferred on NNN medium yielded new promastigotes that were able to proliferate and efficiently infect new cells. HSC are permissive to L. donovani, with neither parasite killing nor apparent cell damage. Thus, HSC could act as potent sanctuary cells for Leishmania in the liver, which could partially explain parasite reactivation after an asymptomatic carriage or a cured visceral leishmaniasis.
ISSN: 0031-1820

inserm-00825803
http://www.hal.inserm.fr/inserm-00825803
DOI : 10.1017/S0031182012001965
PUBMED : 23253952

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND:In French Guiana, a French overseas territory in South America, 6 to 10 thousands undocumented persons work illegally in gold mining sites in the Amazonian forest. Precarious life conditions lead to poor health but few data exist on the health status of illegal gold miners in French Guiana. The objective of this article was to describe the sociodemographic and health status of this vulnerable population.METHOD:A prospective cross-sectional survey was conducted in 2015 on gold mine supply sites at the border between French Guiana and Suriname. Health status was assessed through medical examination, past medical history, haemoglobin concentration, and HIV and malaria testing. A questionnaire was used to collect data about the migration itinerary and life conditions on mining sites.RESULTS:Among the 421 adults included in the study, 93.8% (395/421) were Brazilian, mainly from Maranhão (55.7%, 220/395), the poorest Brazilian state. The sex ratio was 2.4. Overall, 48% of persons never went to school or beyond the primary level. The median time spent in gold mining was quite long (10 years), with a high turn-over. One third of the surveyed population (37.1%, 156/421) had high blood pressure, and only two had a medical follow-up. Most persons had experienced malaria (89.3%, 376/421). They declared frequent arboviroses and digestive disorders. Active leishmaniasis was observed in 8.3% of gold miners. Among women, 28.5% were anemic. Concerning HIV, 36.6% (154/421) of persons, mainly men, never got tested before and 6 were tested positive, which represented an HIV prevalence of 1.43% (95%CI =0.29-2.5).CONCLUSION:These findings support the hypothesis that mining in remote areas is linked to several specific illnesses. Theoretically, gold miners would be presumed to start their economical migration to French Guiana as a healthy group. However, their strenuous working and living conditions there lead to poor health caused by infectious and non infectious diseases. This description of their health status is precious for health policy planners in French Guiana given the importance of controlling communicable disease, and the severity and range of specific illnesses acquired by this neglected population.TRIAL REGISTRATION:Clinical trial registration PRS N° NCT02903706 . Retrospectively registered 09/13/2016.
ISSN: 1471-2458

inserm-01566314
http://www.hal.inserm.fr/inserm-01566314
http://www.hal.inserm.fr/inserm-01566314/document
http://www.hal.inserm.fr/inserm-01566314/file/2017%2C%20Douine%20-%20Illegal%20gold%20miners%20in%20French%20Guiana.pdf
DOI : 10.1016/S0140-6736(10)62169-1

Éditeur(s) : HAL CCSD American Medical Association (AMA)
Résumé : International audience
IMPORTANCE Although frequently used in treating intensive care unit (ICU) patients with sepsis, empirical antifungal therapy, initiated for suspected fungal infection, has not been shown to improve outcome. OBJECTIVE To determine whether empirical micafungin reduces invasive fungal infection (IFI)-free survival at day 28. DESIGN, SETTING, AND PARTICIPANTS Multicenter double-blind placebo-controlled study of 260 nonneutropenic, nontransplanted, critically ill patients with ICU-acquired sepsis, multiple Candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between July 2012 and February 2015 in 19 French ICUs. INTERVENTIONS Empirical treatment with micafungin (100mg, once daily, for 14 days) (n = 131) vs placebo (n = 129). MAIN OUTCOMES AND MEASURES The primary end pointwas survival without proven IFI 28 days after randomization. Key secondary end points included new proven fungal infections, survival at day 28 and day 90, organ failure, serum (1-3)-beta-D-glucan level evolution, and incidence of ventilator-associated bacterial pneumonia. RESULTS Among 260 patients (mean age 63 years; 91 [35%] women), 251 (128, micafungin group; 123, placebo group) were included in the modified intent-to-treat analysis. Median values were 8 for Sequential Organ Failure Assessment (SOFA) score, 3 for number of Candida-colonized sites, and 99 pg/mL for level of (1-3)-beta-D-glucan. On day 28, there were 82 (68%) patients in the micafungin group vs 79 (60.2%) in the placebo group who were alive and IFI free (hazard ratio [HR], 1.35 [95% CI, 0.87-2.08]). Results were similar among patients with a (1-3)-beta-D-glucan level of greater than 80 pg/mL (n = 175; HR, 1.41 [95% CI, 0.85-2.33]). Day-28 IFI-free survival in patients with a high SOFA score (> 8) was not significantly different when compared between the micafungin vs placebo groups (HR, 1.69 [95% CI, 0.96-2.94]). Use of empirical micafungin decreased the rate of new invasive fungal infection in 4 of 128 patients (3%) in the micafungin group vs placebo (15/123 patients [12%]) (P =.008). CONCLUSIONS AND RELEVANCE Among nonneutropenic critically ill patients with ICU-acquired sepsis, Candida species colonization at multiple sites, and multiple organ failure, empirical treatment with micafungin, compared with placebo, did not increase fungal infection-free survival at day 28.
ISSN: 0098-7484

hal-01405822
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01405822
DOI : 10.1001/jama.2016.14655
PUBMED : 27706483

Éditeur(s) : HAL CCSD SAGE Publications
Résumé : International audience
In Western French Guiana there was a dramatic increase in HIV-prevalence between 1990 and 2000. The present study describes the causes of fever among HIV patients hospitalized in the medical ward of the only hospital in the western part of French Guiana. A retrospective descriptive study was conducted between January 1st 2008 and June 30th 2010 in the department of medicine of Saint Laurent du Maroni Hospital. The main characteristics of 67 patients having presented with fever in the first 48 hours of hospitalization were described. Among patients with CD4<200/mm3 the main febrile opportunistic infection was disseminated histoplasmosis (41.1%). Among patients with CD4 counts <50/mm3 and fever without focal points 85.7% had disseminated histoplasmosis. Three patients died and all had disseminated histoplasmosis. Disseminated histoplasmosis is the most common febrile opportunistic infection in western French Guiana. Primary prophylaxis with itraconazole among immunocompromised patients seems warranted.
ISSN: 0956-4624

inserm-01082409
http://www.hal.inserm.fr/inserm-01082409
http://www.hal.inserm.fr/inserm-01082409/document
http://www.hal.inserm.fr/inserm-01082409/file/2014%2C%20Vantilcke%20-%20Fever%20and%20HIV.pdf
http://www.hal.inserm.fr/inserm-01082409/file/Histoplasmosis_tab_2%5B1%5D%20revised.pdf

Éditeur(s) : HAL CCSD American Society for Investigative Pathology (ASIP)
Résumé : International audience
Semen represents the main vector of HIV dissemination worldwide, yet the origin of HIV in semen remains unclear. Viral populations distinct from those found in blood have been observed in semen, indicating local viral replication within the male genital tract. The seminal vesicles, the secretions of which constitute more than 60% of the seminal fluid, could represent a major source of virus in semen. This study is the first to investigate the susceptibility of human seminal vesicles to HIV infection both in vitro and in vivo. We developed and characterized an organotypic culture of human seminal vesicles to test for target cells and HIV infection, and, in parallel, analyzed the seminal vesicle tissues from HIV-infected donors. In vitro, in contrast to HIV-1 X4, HIV-1 R5 exposure induced productive infection. Infected cells consisted primarily of resident CD163(+) macrophages, often located close to the lumen. In vivo, HIV protein and RNA were also detected primarily in seminal vesicle macrophages in seven of nine HIV-infected donors, some of whom were receiving prolonged suppressive highly active antiretroviral therapy. These results demonstrate that human seminal vesicles support HIV infection in vitro and in vivo and, therefore, have the potential to contribute virus to semen. The presence of infected cells in the seminal vesicles of treated men with undetectable viremia suggests that this organ could constitute a reservoir for HIV.
American Journal of Pathology

inserm-00626549
http://www.hal.inserm.fr/inserm-00626549
DOI : 10.1016/j.ajpath.2011.08.005
PUBMED : 21925468

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
OBJECTIVES: The ANRS-112 INTERPRIM trial assessed whether fixed-cycles of antiretroviral treatment interruption (ART-STI) combined or not with pegylated interferon alpha-2b (peg-IFN) could lower viral load and achieve a healthier immune system in patients diagnosed during primary HIV-1-infection (PHI). DESIGN AND METHODS: Patients were randomized to receive either continuous ART (cART) during 72 weeks, or cART during 36 weeks followed by three ART-STIs, or the same ART-STIs associated with peg-IFN during the first 14 weeks and each interruption (ART-STI-IFN). Treatment was stopped at week 72. Final evaluation was based on plasma HIV-RNA level 6 months after the last treatment interruption. RESULTS: Eighty-seven percent of patients achieved undetectable HIV-RNA at week 32, with no deleterious impact of sequential treatment interruptions (STIs). Viral rebounds during interruptions were lower in the ART-STI-IFN than in the ART-STI group and during the second and third interruptions compared with the first one. However, HIV-RNA levels, CD4 T-cell counts and CD4 T/CD8 T ratios were similar between groups after the 6-month interruption, with a persistent effect on CD4 T cells and total cell-associated HIV-DNA levels. Predictive factors of virological outcome were HIV-RNA and HIV-DNA levels at PHI and HIV-DNA levels at treatment interruption. HIV-specific responses did not differ between strategies and were not associated with outcome. Forty-eight percent of patients experienced treatment resumption during long-term follow-up without difference between groups. CONCLUSION: When initiated during PHI, STIs associated or not with IFN did not result in a different outcome as compared to cART. All regimens showed a high response rate and a sustained immunological benefit after cessation.
ISSN: 0269-9370

hal-00875175
https://hal.archives-ouvertes.fr/hal-00875175
DOI : 10.1097/QAD.0b013e32835844d9
PUBMED : 22842994

Éditeur(s) : HAL CCSD
Résumé : International audience
The increasing development of world trade has promoted the spread of diseases. Recent events, like the H1N1 outbreak and spread, have confirmed this tendency. Everyone could observe that this kind of infectious disease often has the ability to cross countries borders and spread rapidly. Preventing, monitoring and controlling the outbreak of these diseases have appeared to be a public health problem of primary importance for years. However, although numerous works have been conducted in order to understand and study epidemics, this subject remains a topical issue because of the complexity of the phenomena. In this paper, we present new opportunities offered by the field of social networks for understanding the spread of infectious diseases. This work focuses both on techniques already used in epidemiology, and very recent works in social network analysis that open new perspectives. We give an overview of methods currently used to model and study the spread of diseases and future directions that the social network approach allows to glimpse.
2011 Fifth International Conference on Research Challenges in Information Science (RCIS)
Gosier, Guadeloupe

hal-00624364
https://hal.archives-ouvertes.fr/hal-00624364
DOI : 10.1109/RCIS.2011.6006866

Éditeur(s) : HAL CCSD
Résumé : Visceral leishmaniasis is a life-threatening systemic disease caused by Leishmania protozoans, L. donovani and L. infantum, which invade mononuclear phagocytes in the lymphoid organs and the liver. The control of the hepatic parasite burden depends on the granuloma formation, which is favored by a Th1 immune response in a Th2 tissue microenvironment. The aim of this work was to study the role of the recently described Th2 cytokine IL-33 in this complex immune response, which remains partially misunderstood. IL-33 dosages in different patient sera and IL-33+ cells detected in the liver of a patient from Rennes suggested that IL-33 could be a biomarker for active visceral leishmaniasis. As IL-33 was described in hepatic stellate cells during chronic hepatitis, these cells were exposed to L. donovani in primary culture. The cell permissivity to L. donovani and the parasite persistence during a long term culture led us to propose hepatic stellate cells as a new type of sanctuary cells, which could partially explain asymptomatic carriage. However, these cells were apparently not the main source of IL-33 during visceral leishmaniasis. In infected BALB/c and C57BL/6 mice, IL-33 was detected in the liver in non stellate cells preferentially localized in granulomas. The presence of cells expressing its specific receptor ST2 in the liver led us to explore the role of the IL-33/ST2 axis. BALB/c mice deficient in ST2 or treated with recombinant IL-33 and infected with L. donovani revealed that IL-33 downregulates the expression of Th1 key cytokines (IL-12, IFN-γ) and the recruitment of neutrophils and monocytes. Finally, IL-33 acts as a susceptibility factor during visceral leishmaniasis. Besides, the model of L. donovani infected C57BL/6 mice deficient in IL-33 or treated with recombinant IL-33 suggests possible differential roles of IL-33 depending on the immune environment related to the host genetic background.
La leishmaniose viscérale est une maladie systémique mortelle en l’absence de traitement. Elle est due aux protozoaires Leishmania donovani et L. infantum, parasites des phagocytes mononucléés, capables d’envahir les organes lymphoïdes et le foie. Le contrôle de l’infection hépatique repose sur la mise en place d’une réponse granulomateuse efficace, promue par une réponse immunitaire Th1, dans un environnement tissulaire Th2. L’objectif de ce travail était l'étude du rôle d’une cytokine Th2 récemment décrite, l’IL-33, dans cette réponse hépatique complexe encore partiellement incomprise. Des dosages d’IL-33 sur des sérums de patients et la détection de cellules IL-33+ dans le foie d’un patient rennais ont placé l’IL-33 comme un biomarqueur possible de la maladie active. L’IL-33 étant exprimée dans les cellules étoilées du foie au cours d’hépatites chroniques, ces cellules ont été exposées à L. donovani. Leur permissivité aux leishmanies sans toxicité apparente ni perturbation de leurs propriétés fonctionnelles, ainsi que la persistance des leishmanies sur une culture de plusieurs semaines, nous ont conduit à proposer les cellules étoilées comme cellules sanctuaires possibles pour les leishmanies viscérotropes, contribuant donc potentiellement au portage asymptomatique. En revanche, elles ne sont pas apparues comme une source majeure d'IL-33 au cours de la leishmaniose viscérale. Chez des souris C57BL/6 et BALB/c infectées par L. donovani, l'IL-33 a été observée dans des cellules ne s'apparentant pas à des cellules étoilées, et principalement localisées dans les granulomes. Des cellules exprimant son récepteur ST2 ayant été également observées dans le foie, un rôle de l’axe IL-33/ST2 a été recherché. Les résultats obtenus chez des souris BALB/c déficientes en ST2 ou traitées par de l'IL-33 recombinante suggèrent que l'IL-33 régule négativement l'expression de cytokines Th1 (IL-12, IFN-γ) et l'infiltrat de neutrophiles et monocytes dans le foie, limitant ainsi le contrôle de la charge parasitaire. Ainsi, l'IL-33 semble être un facteur de susceptibilité pour la leishmaniose viscérale. En parallèle, des travaux entrepris sur des souris C57BL/6 infectées par L. donovani suggèrent de possibles rôles différentiels de l'IL-33 en fonction de l'environnement immunitaire inhérent au fond génétique de l'hôte.
https://tel.archives-ouvertes.fr/tel-01126847

Droits : info:eu-repo/semantics/OpenAccess
NNT : 2013REN1B002
tel-01126847
https://tel.archives-ouvertes.fr/tel-01126847
https://tel.archives-ouvertes.fr/tel-01126847/document
https://tel.archives-ouvertes.fr/tel-01126847/file/2013REN1B002.pdf

Éditeur(s) : HAL CCSD
Résumé : Hepatitis C virus (HCV) is one of the leading causes of hepatocellular carcinoma. Therapeutic treatment against the virus has been recently improved by a tritherapy including pegylated interferon, ribavirin and antiviral protease. Nevertheless, the importance of side effects and the emergence of resistant mutants require the development of new antivirals. In this context, our team has recently discovered that Type III phosphatidylinositol 4-kinases (PI4KIIIα and PI4KIIIβ) are essential for the propagation of the virus in a human hepatic cell line at the entry and replication steps. To further characterize these potential therapeutic targets, we investigate the implication of these kinases during the HCV entry, using primary human hepatocytes, a model closer to the in vivo conditions. Two lines of research were developed: Verification of the importance of the kinase activity of PI4KIIIs during HCV entry in primary human hepatocytes, through a chemical approach; Validation of the involvement of these kinases and their enzymatic activity during viral entry through a genetic approach based on RNA interference and phenotype rescue. In parallel, we studied the expression of PI4KIIIα in liver diseases. Our results suggest the involvement of PI4KIIIα in HCV entry; the involvement of PI4KIIIIβ needs to be confirmed. The analysis of PI4KIIIα expression in hepatocellular carcinoma led us to propose this kinase as a new molecular marker, which could improve the already established prognosis models and could lead to the development of new therapeutic approaches.
Le virus de l’hépatite C (VHC) est l’un des principaux facteurs étiologiques du carcinome hépatocellulaire. Le traitement des hépatites virales C a été récemment amélioré grâce à une trithérapie (interféron, ribavirine et anti-protéase virale). Néanmoins l’importance des effets secondaires et l’émergence de mutants résistants nécessitent de découvrir de nouveaux antiviraux. Dans ce contexte, notre équipe a récemment découvert que les phosphatidylinositol 4-kinases de type III (PI4KIIIα et PI4KIIIβ) étaient indispensables à la propagation du virus dans une lignée hépatique humaine, et ce, à 2 étapes de son cycle biologique : l’entrée et la réplication. L’objectif du présent travail était de poursuivre la validation de ces nouvelles cibles thérapeutiques potentielles, en approfondissant nos connaissances sur la dépendance du virus à l’égard de ces kinases au cours de son entrée. Pour cela, nous avons utilisé le modèle des hépatocytes humains primaires, système in vitro plus proche du contexte physiologique que les modèles utilisés jusqu’à présent et qui étaient basés sur l’exploitation de lignées. Deux axes ont été développés : Vérification de l’importance de l’activité kinase des PI4KIIIs au cours de l’entrée du VHC dans les hépatocytes humains primaires, à travers une approche chimique ; Validation de l’implication de ces kinases et de leur activité enzymatique au cours de l’entrée virale grâce à une approche génétique basée sur l’ARN interférence et la restauration de phénotype. En parallèle, nous avons étudié l’expression de PI4KIIIα au cours de pathologies hépatiques. Nos résultats suggèrent une implication de PI4KIIIα au cours de l’entrée du VHC dans les hépatocytes humains primaires, mais restent à confirmer quant à l’implication de PI4KIIIβ. Par ailleurs, l’analyse de l’expression de PI4KIIIα dans le carcinome hépatocellulaire (CHC) conduit à proposer cette kinase comme un nouveau marqueur moléculaire, qui pourrait améliorer les modèles de pronostic déjà établis et pourrait conduire au développement de nouvelles approches thérapeutiques pour les patients atteints d’un CHC, quelque soit l’étiologie.
https://tel.archives-ouvertes.fr/tel-00950335

Droits : info:eu-repo/semantics/OpenAccess
NNT : 2013REN1B006
tel-00950335
https://tel.archives-ouvertes.fr/tel-00950335
https://tel.archives-ouvertes.fr/tel-00950335/document
https://tel.archives-ouvertes.fr/tel-00950335/file/ILBOUDOAdeodat.pdf

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population. HIV type 1-infected patients who previously failed ≥12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single-arm, phase 2 trial. Patients with cirrhosis and previous null response were excluded. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz, atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 µg/week) plus RBV (1000-1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125 mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV for 32-56 weeks according to virological response at week 8. The primary endpoint was the SVR rate at 24 weeks after the end of treatment (SVR24). Sixty-nine patients started treatment; SVR24 was achieved in 55 (80% [95% confidence interval, 68%-88%). SVR24 was not influenced by baseline fibrosis stage, IL28B genotype, antiretroviral regimen, HCV subtype, CD4 cell count, previous response to HCV treatment, HCV RNA level, or HCV RNA decline at week 4. HCV treatment was discontinued for adverse events (AEs) in 20% of patients, including cutaneous (4%), psychiatric (4%), hematological (6%), and other AEs (6%). Peg-IFN or RBV dose reduction was required in 23% and 43% of patients, respectively. Seventy percent of patients required erythropoietin, blood transfusions, or RBV dose reduction for anemia. Two patients died during the study. No HIV breakthrough was observed. Despite a high discontinuation rate related to toxicity, a substantial proportion of treatment-experienced HIV-coinfected patients achieved SVR24 with a telaprevir-based regimen. Clinical Trials Registration. NCT01332955.
ISSN: 1058-4838

hal-01118447
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118447
PUBMED : 25139963
DOI : 10.1093/cid/ciu659

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
We carried out a soil sampling survey in September 2008 in central Cayenne, French Guiana, using molecular methods to assess the presence of the dimorphic fungus Histoplasma capsulatum. Four of the 31 samples collected (12.9 %) tested positive by PCR, with confirmation of the result by DNA sequencing. H. capsulatum is therefore present in urban environments in French Guiana. These results provide additional support for the primary prophylaxis of AIDS-related histoplasmosis in French Guiana
ISSN: 0301-486X

hal-01349668
https://hal.archives-ouvertes.fr/hal-01349668
https://hal.archives-ouvertes.fr/hal-01349668/file/Article%20Histo%20Cayenne%20R2.pdf
DOI : 10.1007/s11046-012-9550-y